RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer.
Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer.
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炎症性肠病(IBD)是一组因宿主肠道菌群免疫反应异常而导致肠道炎症和病变的疾病。皮质类固醇、抗炎药和抗生素常用于减轻非特异性炎症和降低复发率;然而,此类治疗随着时间推移会失效。慢性结肠炎患者更易发展为结直肠癌,尤其是结肠炎病程较长者。化疗常因副作用而使用受限,导致疗效降低,因此迫切需要改进治疗并寻找新的治疗靶点。近年来,肿瘤免疫治疗取得了重大进展,主要分为癌症疫苗、过继性细胞免疫治疗或免疫检查点阻断疗法。检查点标志物在癌细胞上表达以逃避免疫系统,因此检查点抑制剂在过去5-10年间改变了癌症治疗格局。免疫检查点抑制剂在单药和联合治疗中均产生了持久的临床应答。Winnie小鼠是一种可行的自发性慢性结肠炎模型,其免疫反应与人类IBD相似。测定这些小鼠组织中的检查点标志物表达水平,将有助于深入了解疾病的发生、进展和癌变。此类信息将有助于识别新的检查点标志物,并开发使用或不使用免疫检查点抑制剂或疫苗的治疗方法,以减缓或阻止疾病进展。
Inflammatory Bowel Disease (IBD) is a group of diseases that cause intestinal inflammation and lesions because of an abnormal immune response to host gut microflora. Corticosteroids, anti-inflammatories, and antibiotics are often used to reduce non-specific inflammation and relapse rates; however, such treatments are ineffective over time. Patients with chronic colitis are more susceptible to developing colorectal cancer, especially those with a longer duration of colitis. There is often a limit in using chemotherapy due to side effects, leading to reduced efficacy, leaving an urgent need to improve treatments and identify new therapeutic targets. Cancer immunotherapy has made significant advances in recent years and is mainly categorized as cancer vaccines, adoptive cellular immunotherapy, or immune checkpoint blockade therapies.
Checkpoint markers are expressed on cancer cells to evade the immune system, and as a result checkpoint inhibitors have transformed cancer treatment in the last 5-10 years. Immune checkpoint inhibitors have produced long-lasting clinical responses in both single and combination therapies. Winnie mice are a viable model of spontaneous chronic colitis with immune responses like human IBD.
Determining the expression levels of checkpoint markers in tissues from these mice will provide insights into disease initiation, progression, and cancer. Such information will lead to identification of novel checkpoint markers and the development of treatments with or without immune checkpoint inhibitors or vaccines to slow or stop disease progression.
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